Many methods are known for the topical treatment of fungal infections, including the use of antibiotics (e.g. nystatin and amphotericin B), imidazole antifungal agents such as miconazole, clotrimazole, econazole and sulconazole, and non-imidazole fungal agents such as the allylamine derivatives terbinafine and naftifine, and the benzylamine butenafine.
Recently, the combination of imidazole antifungal agents with a corticosteroid has been disclosed for the topical treatment of fungal diseases. The purpose of the steroid is to alleviate the symptoms of erythma and the related itching that are normally associated with fungal infections. Additionally, steroids may also induce fungal spores to be more sensitive to treatment by an antifungal agent.
However, the disadvantage of such a combination is that it is undesirable to use steroids for topical treatment for extended periods of time. Steroids can penetrate the skin and cause undesirable side effects, including skin atrophy, suppression of the hypothalamic-pituitary-adrenal axis, Cushing's syndrome, glucosuria, hyperglycemia, etc. Additionally, the addition of a steroid may actually decrease the effectiveness of some antifungal compounds, because of the potential of steroids to function as a deactivating agent. Additionally, some antifungal compounds are quite toxic in their own right.
Currently, the commercially available products that contain a mixture of an antifungal and a steroid are Lotrisone cream (clotrimazole 1%/betamethasone dipropionate 0.064%), Daktacort cream (miconazole nitrate 2%/hydrocortisone 1%) and Canesten HC cream (clotrimazole 1%/hydrocortisone 1%). However, as a consequence of the prolonged time necessary to effect successful treatment, these products exhibit the undesirable side effects noted above.
It would therefore be advantageous to have a formulation that retains the advantages of combining an agent useful for treating fungal diseases with a steroid capable of reducing the associated inflammation, with the ability to rapidly eradicate fungal infections and eliminate the symptoms thereof, and as a consequence minimize the risk of undesirable side effects. Such a formulation would ideally deliver the antifungal agent and the steroid to the skin, and maintain the combination on the skin for the period of time necessary to effect treatment, but minimize the penetration of the skin with respect to the active ingredients, thus avoiding the potential steroid side effects noted above. Surprisingly, we have discovered such a formulation.
Relevant Literature
Combinations of antifungals and steroids are disclosed in U.S. Pat. Nos. 4,912,124, 5,002,938, 5,021,458, 5,110,809, 5,174,475, 5,219,877, 5,407,663, and 5,310,545,